1,3-difluoro-2-methylbenzene

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 1,3-difluoro-2-methylbenzene (5.00 g, 39.0 mmol), chlorosulfuric acid (10.5 mL, 158 mmol) was added with cooling on ice, and the mixture was stirred at room temperature for 5 hours. To the reaction solution, water (100 mL) was added with cooling on ice, followed by extraction with dichloromethane (100 mL). The thus obtained organic layer was dried over anhydrous sodium sulfate. After vacuum concentration, the residue was purified with silica gel chromatography to yield the title compound (8.65 g, 98%) as a colorless amorphous solid. with cooling on ice with cooling on ice followed by extraction with dichloromethane (100 mL) The thus obtained organic layer was dried over anhydrous sodium sulfate After vacuum concentration the residue was purified with silica gel chromatography

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 1,3-difluoro-2-methyl-benzene (15 g, 0.12 mol) in conc. H2SO4 (100 mL) was treated drop wise with 65% HNO3 (11.4 g, 0.12 mol) at −10° C. and the resultant mixture was stirred for about 30 min. The mixture was poured into ice-water and extracted with ethyl acetate (3×200 mL). The combined organic layers were washed with brine, dried (Na2SO4) and concentrated in vacuo to give 1,3-difluoro-2-methyl-4-nitro-benzene (16 g, 78% yield) 1H NMR (400 MHz, CDCl3): δ 7.80 (m, 1 H), 6.95 (m, 1H), 2.30 (s, 3 H). extracted with ethyl acetate (3×200 mL) The combined organic layers were washed with brine dried (Na2SO4) concentrated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 1,3-difluoro-2-methyl-benzene (15 g, 0.12 mol) in H2SO4 (100 mL) was treated dropwise with 65% HNO3 (11.4 g, 0.12 mol) at −10° C. and the resultant mixture was stirred for about 30 min. The mixture was poured into ice-water and extracted with ethyl acetate (3×200 mL). The combined organic layers were washed with brine, dried (Na2SO4) and concentrated in vacuo to give 1,3-difluoro-2-methyl-4-nitro-benzene (16 g, 78% yield). 1H NMR (400 MHz, CDCl3): δ 7.80 (m, 1H), 6.95 (m, 1H), 2.30 (s, 3H). extracted with ethyl acetate (3×200 mL) The combined organic layers were washed with brine dried (Na2SO4) concentrated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 1,3-difluoro-2-methyl-benzene (15 g, 0.12 mol) in H2SO4 (100 mL) was treated dropwise with 65% HNO3 (11.4 g, 0.12 mol) at −10° C. and the resultant mixture was stirred for about 30 min. The mixture was poured into ice-water and extracted with ethyl acetate (3×200 mL). The combined organic layers were washed with brine, dried (Na2SO4) and concentrated in vacuo to give 1,3-difluoro-2-methyl-4-nitro-benzene (16 g, 78% yield). 1H NMR (400 MHz, CDCl3): δ 7.80 (m, 1H), 6.95 (m, 1H), 2.30 (s, 3H). extracted with ethyl acetate (3×200 mL) The combined organic layers were washed with brine dried (Na2SO4) concentrated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 1,3-difluoro-2-methylbenzene (5.00 g, 39.0 mmol), chlorosulfuric acid (10.5 mL, 158 mmol) was added with cooling on ice, and the mixture was stirred at room temperature for 5 hours. To the reaction solution, water (100 mL) was added with cooling on ice, followed by extraction with dichloromethane (100 mL). The thus obtained organic layer was dried over anhydrous sodium sulfate. After vacuum concentration, the residue was purified with silica gel chromatography to yield the title compound (8.65 g, 98%) as a colorless amorphous solid. with cooling on ice with cooling on ice followed by extraction with dichloromethane (100 mL) The thus obtained organic layer was dried over anhydrous sodium sulfate After vacuum concentration the residue was purified with silica gel chromatography

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 1,3-difluoro-2-methylbenzene (5.00 g, 39.0 mmol), chlorosulfuric acid (10.5 mL, 158 mmol) was added with cooling on ice, and the mixture was stirred at room temperature for 5 hours. To the reaction solution, water (100 mL) was added with cooling on ice, followed by extraction with dichloromethane (100 mL). The thus obtained organic layer was dried over anhydrous sodium sulfate. After vacuum concentration, the residue was purified with silica gel chromatography to yield the title compound (8.65 g, 98%) as a colorless amorphous solid. with cooling on ice with cooling on ice followed by extraction with dichloromethane (100 mL) The thus obtained organic layer was dried over anhydrous sodium sulfate After vacuum concentration the residue was purified with silica gel chromatography

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 1,3-difluoro-2-methyl-benzene (15 g, 0.12 mol) in H2SO4 (100 mL) was treated drop-wise with 65% HNO3 (11.4 g, 0.12 mol) at −10° C. and the resultant mixture was stirred for 30 min. The mixture was poured into ice-water and extracted with EtOAc (3×). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated in vacuo to give 1,3-difluoro-2-methyl-4-nitro-benzene (16 g, 78%). 1H NMR (400 MHz, CDCl3): δ 7.80 (m, 1 H), 6.95 (m, 1 H), 2.30 (s, 3H). extracted with EtOAc (3×) The combined organic layers were washed with brine dried over Na2SO4 concentrated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 1,3-difluoro-2-methyl-benzene (15 g, 0.12 mol) in H2SO4 (100 mL) was treated dropwise with 65% HNO3 (11.4 g, 0.12 mol) at −10° C. and the resultant mixture was stirred for about 30 min. The mixture was poured into ice-water and extracted with ethyl acetate (3×200 mL). The combined organic layers were washed with brine, dried (Na2SO4) and concentrated in vacuo to give 1,3-difluoro-2-methyl-4-nitro-benzene (16 g, 78% yield). 1H NMR (400 MHz, CDCl3): δ 7.80 (m, 1H), 6.95 (m, 1H), 2.30 (s, 3H). extracted with ethyl acetate (3×200 mL) The combined organic layers were washed with brine dried (Na2SO4) concentrated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 1,3-difluoro-2-methylbenzene (15 g, 0.12 mol) in H2SO4 (100 mL) was treated dropwise with HNO3 (65%, 11.4 g, 0.12 mol) at −10° C. The resultant mixture was stirred for about 30 min. The mixture was poured into ice-water and extracted with EtOAc (3×200 mL). The combined organics were washed with brine, dried (NaSO4) and concentrated in vacuo to give 1,3-difluoro-2-methyl-4-nitrobenzene (16 g, 78% yield). 1H NMR (400 MHz, CDCl3) δ 7.80 (m, 1H), 6.8-7.1 (m, 1H), 2.30 (s, 3H). extracted with EtOAc (3×200 mL) The combined organics were washed with brine dried (NaSO4) concentrated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 1,3-difluoro-2-methylbenzene (15 g, 0.12 mol) in H2SO4 (100 mL) was treated dropwise with HNO3 (65%, 11.4 g, 0.12 mol) at −10° C. The resultant mixture was stirred for about 30 min. The mixture was poured into ice-water and extracted with EtOAc (3×200 mL). The combined organics were washed with brine, dried (NaSO4) and concentrated in vacuo to give 1,3-difluoro-2-methyl-4-nitrobenzene (16 g, 78% yield). 1H NMR (400 MHz, CDCl3) δ 7.80 (m, 1H), 6.8-7.1 (m, 1H), 2.30 (s, 3H). extracted with EtOAc (3×200 mL) The combined organics were washed with brine dried (NaSO4) concentrated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 1,3-difluoro-2-methyl-benzene (15 g, 0.12 mol) in conc. H2SO4 (100 mL) was treated drop wise with 65% HNO3 (11.4 g, 0.12 mol) at −10° C. and the resultant mixture was stirred for about 30 min. The mixture was poured into ice-water and extracted with ethyl acetate (3×200 mL). The combined organic layers were washed with brine, dried (Na2SO4) and concentrated in vacuo to give 1,3-difluoro-2-methyl-4-nitro-benzene (16 g, 78% yield) 1H NMR (400 MHz, CDCl3): δ 7.80 (m, 1 H), 6.95 (m, 1H), 2.30 (s, 3 H). extracted with ethyl acetate (3×200 mL) The combined organic layers were washed with brine dried (Na2SO4) concentrated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 1,3-difluoro-2-methyl-benzene (15 g, 0.12 mol) in H2SO4 (100 mL) was treated dropwise with 65% HNO3 (11.4 g, 0.12 mol) at −10° C. and the resultant mixture was stirred for about 30 min. The mixture was poured into ice-water and extracted with ethyl acetate (3×200 mL). The combined organic layers were washed with brine, dried (Na2SO4) and concentrated in vacuo to give 1,3-difluoro-2-methyl-4-nitro-benzene (16 g, 78% yield). 1H NMR (400 MHz, CDCl3): δ 7.80 (m, 1H), 6.95 (m, 1H), 2.30 (s, 3H). extracted with ethyl acetate (3×200 mL) The combined organic layers were washed with brine dried (Na2SO4) concentrated in vacuo